Intermediate Uveitis Clinical Presentation
- Author: Robert H Janigian, Jr, MD; Chief Editor: Hampton Roy, Sr, MD more...
The most common symptoms of intermediate uveitis are blurry vision and floaters.
Pain and photophobia are the exception.
Bilateral involvement at initial presentation approaches 80%, although it is frequently asymmetric. Eventually, approximately one third of unilateral cases will become bilateral.
Later in the disease course, more severe visual loss may occur secondary to chronic CME (28-50%), uveitic glaucoma (15%), rhegmatogenous retinal detachment (3-22%), vitreous hemorrhage (6-28%), cataracts (15-20%), or cyclitic membrane development.
See the list below:
On ocular examination, the ophthalmologist encounters vitritis that ranges in severity. The absence of cellular activity in the vitreous precludes the diagnosis of active intermediate uveitis.
The presenting visual acuity is often reduced to 20/40 (mild visual loss) due to mild vitritis and CME.
Anterior segment inflammation is infrequent and more commonly associated with pediatric intermediate uveitis. On occasion, patients with MS develop granulomatous anterior uveitis with characteristic mutton keratic precipitates.
Aggregates of inflammatory cells may appear in the inferior vitreous as white or yellow tufts termed vitreous snowballs. A snowbank, the requisite finding in pars planitis, may be seen as a grayish yellow exudate along the inferior ora serrata, frequently extending over the pars plana. Not all patients with intermediate uveitis manifest snowbanks.
- In severe cases, the exudates may coalesce across the entire periphery for 360°, albeit rarely.
- Scleral depression is usually required to appreciate snowbanks, but, sometimes, they can be seen with the eye infraducted using an indirect ophthalmoscope without the 20 D-lens.
- In fact, snowbanks may be fibroglial masses and not a true protein exudate (see Histologic Findings).
Peripheral retinal vascular abnormalities are not uncommon but may become obscured by the dense vitritis.
- Sheathing or obliteration of small venules may be noted. This finding may appear months or years after initial presentation.
- Less often, a periarteritis or a combined perivasculitis is present with exudates.
- Peripheral retinal neovascularization can occur as a result of ischemia, causing vitreous hemorrhages; this occurs more commonly in children.
- The neovascularization can evolve into a vascular cyclitic membrane in the rare patient, exercising traction on the ciliary body and leading to hypotony and phthisis bulbi.
CME may be seen. Severe macular edema can be appreciated clinically. Angiographic study or optical coherence tomography is often necessary for a definitive diagnosis, especially if the edema is subtle or if the media are hazy. Some patients with angiographic CME may present with 20/20 acuity.
- Estimates of the incidence of macular edema vary.
- Most early reports have noted this complication in 28-50% of cases.
Optic nerve edema is not uncommon, especially in pediatric cases where the disk is edematous at least half of the time. In a retrospective study, optic disk edema was found in 71% of patients with onset of the disease before age 16 years.
In the anterior segment, late findings include anterior and posterior synechiae, band keratopathy, cataracts, and glaucoma.
- The glaucoma may be related to both the uveitis and/or corticosteroid use.
- The incidence of cataract formation, most often a posterior subcapsular opacity, has been reported in approximately 15-20% of cases and may not be independent to the use of steroids for treatment.
The late complications of intermediate uveitis are important to recognize early.
- A combination of vitreous hemorrhage and vitreous fibrosis can cause traction on the peripheral retina and lead to retinal detachment. Studies vary widely in the frequency of this late complication, ranging from 3-22%. Some detachments may become complete, leading to a phthisical eye.
- Chronic CME may cause moderate-to-severe vision loss. Treating CME, regardless of how good the vision may be, is therefore imperative.
- Peripheral retinal neovascularization can occur as a result of ischemia, causing vitreous hemorrhages, as discussed above.
- A vascular cyclitic membrane can exercise traction on the ciliary body and lead to hypotony and phthisis bulbi.
The cause of intermediate uveitis or pars planitis has not been elucidated. Intermediate uveitis is a category of uveitis based on an anatomical classification system that can include diseases of various etiology and clinical manifestations. Associations of the disease with such entities as MS, sarcoidosis, or inflammatory bowel disease suggest an autoimmune component in at least a subset of patients. The clustering of familial cases has led to the investigation of human leukocyte antigen (HLA) associations. The inciting event appears to be peripheral retinal perivasculitis and vascular occlusion, leading to ocular inflammation, vitritis, and snowbank formation. The etiology of the antigenic stimulus is not clear and may be either vitreal or perivascular in nature.
In 1963, Kimura and Hogan first noted several members of one family to be afflicted with chronic cyclitis.  Since then, there have been multiple case reports of intermediate uveitis in families, including a case report in identical twins.
- Several studies show that the HLA-DR2 histocompatibility complex gene is associated with intermediate uveitis, suggesting an immunogenetic predisposition for the disorder in some cases.
- In a prospective study of 53 patients with pars planitis by Raja et al, an association was found with the HLA-DR15, a subtype of HLA-DR2. In addition, there was a suggestion that the association was stronger for patients with both pars planitis and MS. This supports previous studies showing a similar relationship.
- Other associations include HLA-A28, HLA-B8, and HLA-B51.
- It is evident that genetics plays some role in the pathophysiology of intermediate uveitis, but the importance remains unclear.
- In addition, cytokine gene polymorphism may be associated with disease development and visual prognosis in patients with intermediate uveitis. In particular, TT homozygotes for the interferon-gamma (INF-gamma) gene may be at a higher risk of disease development and may also run a more severe course.
Despite a high prevalence of intermediate uveitis and pars planitis in uveitis clinics, the causative factors are still unknown. Apart from idiopathic forms of the disease, there are known associations with such entities as MS, sarcoidosis, and inflammatory bowel disease. Evidence of a systemic disorder can be found in up to one third of patients with intermediate uveitis. Infectious etiologies include Epstein-Barr virus (EBV) infection, Lyme disease, human T-cell lymphotrophic virus type1 (HTLV-1) infection, cat scratch disease, and hepatitis C.
- The association between MS and intermediate uveitis is well documented. Raja et al reported a 16.2% prevalence rate of MS in a small population with pars planitis, which agrees with the findings of Malinowski and his colleagues.[2, 3]
- Retinal phlebitis, vitreous cells or snowball opacities, posterior synechiae, iritis, iridocyclitis, and retinal neovascularization are common manifestations of ocular sarcoidosis, which emphasizes the overlap of ophthalmologic signs between idiopathic intermediate uveitis and ocular sarcoidosis.
Kimura SJ, Hogan MJ. Chronic Cyclitis. Arch of Ophthalmol. 1964. 71:193-201.
Raja SC, Jabs DA, Dunn JP, et al. Pars Planitis: Clinical Features and Class II HLA Associations. Ophthalmology. 1999. 106 (3):594-599. [Medline].
Malinowski SM, Pulido JS, Folk JC. Long-term visual outcome and complications associated with pars planitis. Ophthalmology. 1993 Jun. 100(6):818-24; discussion 825. [Medline].
Henderly DE, Haymond RS, Rao NA, et al. The significance of the pars plana exudate in pars planitis. Am J Ophthalmol. 1987 May 15. 103(5):669-71. [Medline].
Rodriguez A, Calonge M, Pedroza-Seres M, et al. Referral Patterns of Uveitis in a Tertiary Care Center. Archives of Ophthalmology. 1996. 114 (5):593-599. [Medline].
Kaplan HJ. Intermediate Uveitis (Pars Planitis, Chronic Cyclitis)- A Four Step Approach to Treatment. Saari KM, ed. Uveitis Update. Amsterdam: Exerpta Medica; 1984. 169-172.
Hogewind BF, Zijlstra C, Klevering BJ, et al. Intravitreal triamcinolone for the treatment of refractory macular edema in idiopathic intermediate or posterior uveitis. Eur J Ophthalmol. 2008 May-Jun. 18(3):429-34. [Medline].
Murphy CC, Greiner K, Plskova J, et al. Cyclosporine vs tacrolimus therapy for posterior and intermediate uveitis. Arch Ophthalmol. 2005 May. 123(5):634-41. [Medline].
Markomichelakis NN, Theodossiadis PG, Pantelia E, et al. Infliximab for chronic cystoid macular edema associated with uveitis. Am J Ophthalmol. 2004 Oct. 138(4):648-50. [Medline].
Rajaraman RT, Kimura Y, Li S, et al. Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology. 2006 Feb. 113(2):308-14. [Medline].
Devenyi RG, Mieler WF, Lambrou FH, et al. Cryopexy of the vitreous base in the management of peripheral uveitis. Am J Ophthalmol. 1988 Aug 15. 106(2):135-8. [Medline].
Park SE, Mieler WF, Pulido JS. 2 peripheral scatter photocoagulation for neovascularization associated with pars planitis. Arch Ophthalmol. 1995 Oct. 113(10):1277-80. [Medline].
Becker M, Davis J. Vitrectomy in the treatment of uveitis. Am J Ophthalmol. 2005 Dec. 140(6):1096-105. [Medline].
Quinones K, Choi JY, Yilmaz T, Kafkala C, Letko E, Foster CS. Pars plana vitrectomy versus immunomodulatory therapy for intermediate uveitis: a prospective, randomized pilot study. Ocul Immunol Inflamm. 2010 Oct. 18(5):411-7. [Medline].
Jaffe GJ, Martin D, Callanan D, et al. Fluocinolone acetonide implant (Retisert) for noninfectious posterior uveitis: thirty-four-week results of a multicenter randomized clinical study. Ophthalmology. 2006 Jun. 113(6):1020-7. [Medline].
Lowder C, Belfort R Jr, Lightman S, Foster CS, Robinson MR, Schiffman RM, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol. 2011 May. 129(5):545-53. [Medline].
Thorne JE, Daniel E, Jabs DA, et al. Smoking as a risk factor for cystoid macular edema complicating intermediate uveitis. Am J Ophthalmol. 2008 May. 145(5):841-6. [Medline].
Kalinina Ayuso V, Ten Cate HA, van den Does P, Rothova A, de Boer JH. Young age as a risk factor for complicated course and visual outcome in intermediate uveitis in children. Br J Ophthalmol. 2011 May. 95(5):646-51. [Medline].
Abu El-Asrar AM, Geboes K. An immunohistochemical study of the 'snowbank' in a case of pars planiti. Ocul Immunol Inflamm. 2002 Jun. 10(2):117-23. [Medline].
Androudi S, Ahmed M, Fiore T, et al. Combined pars plana vitrectomy and phacoemulsification to restore visual acuity in patients with chronic uveitis. J Cataract Refract Surg. 2005 Mar. 31(3):472-8. [Medline].
Becker MD, Heiligenhaus A, Hudde T, et al. Interferon as a treatment for uveitis associated with multiple sclerosis. Br J Ophthalmol. 2005 Oct. 89(10):1254-7. [Medline].
Biswas J, Raghavendran SR, Vijaya R. Intermediate uveitis of pars planitis type in identical twins. Report of a case. Int Ophthalmol. 1998. 22(5):275-7. [Medline].
Bloch-Michel E, Nussenblatt RB. International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol. 1987 Feb 15. 103(2):234-5. [Medline].
Bonfioli AA, Damico FM, Curi AL, et al. Intermediate uveitis. Semin Ophthalmol. 2005 Jul-Sep. 20(3):147-54. [Medline].
Bora NS, Bora PS, Tandhasetti MT, et al. Molecular cloning, sequencing, and expression of the 36 kDa protein present in pars planitis. Sequence homology with yeast nucleopore complex protein. Invest Ophthalmol Vis Sci. 1996 Aug. 37(9):1877-83. [Medline].
Boyd SR, Young S, Lightman S. Immunopathology of the noninfectious posterior and intermediate uveitides. Surv Ophthalmol. 2001 Nov-Dec. 46(3):209-33. [Medline].
Brockhurst RJ, Schepens CL, Okamura ID. Uveitis II. Peripheral Uveitis: Clinical Descriptions, Complications and Differential Diagnosis. Am J Ophthalmol. 1960. 49:1257-1266.
Capone A Jr, Aaberg TM. Intermediate Uveitis. In: Albert, Jacobiec FA, eds. Principles and Practice of Ophthalmology. 1994. Philadelphia: WB Saunders:423-442.
Doro D, Manfre A, Deligianni V, et al. Combined 50- and 20-MHz frequency ultrasound imaging in intermediate uveitis. Am J Ophthalmol. 2006 May. 141(5):953-5. [Medline].
Duguid IG, Ford RL, Horgan SE, et al. Combined orbital floor betamethasone and depot methylprednisolone in uveitis. Ocul Immunol Inflamm. 2005 Feb. 13(1):19-24. [Medline].
Ganesh SK, Babu K, Biswas J. Phacoemulsification with intraocular lens implantation in cases of pars planitis. J Cataract Refract Surg. 2004 Oct. 30(10):2072-6. [Medline].
Guest S, Funkhouser E, Lightman S. Pars planitis: a comparison of childhood onset and adult onset disease. Clin Experiment Ophthalmol. 2001 Apr. 29(2):81-4. [Medline].
Holland GN. The enigma of pars planitis, revisited. Am J Ophthalmol. 2006 Apr. 141(4):729-30. [Medline].
Jabs DA, Nussenblatt RB, Rosenbaum JT, et al. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep. 140(3):509-16. [Medline].
Jain R, Ferrante P, Reddy GT, et al. Clinical features and visual outcome of intermediate uveitis in children. Clin Experiment Ophthalmol. 2005 Feb. 33(1):22-5. [Medline].
Kaplan HJ. Surgical Treatment of Intermediate Uveitis. Developments in Ophthalmology. 1992. 23:185-189. [Medline].
Malik AR, Pavesio C. The use of low dose methotrexate in children with chronic anterior and intermediate uveitis. Br J Ophthalmol. 2005 Jul. 89(7):806-8. [Medline].
Miserocchi E, Baltatzis S, Ekong A, et al. Efficacy and safety of chlorambucil in intractable noninfectious uveitis: the Massachusetts Eye and Ear Infirmary experience. Ophthalmology. 2002 Jan. 109(1):137-42. [Medline].
Murphy CC, Hughes EH, Frost NA, et al. Quality of life and visual function in patients with intermediate uveitis. Br J Ophthalmol. 2005 Sep. 89(9):1161-5. [Medline].
Nussenblatt RB, Peterson JS, Foster CS, et al. Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative interventional case series. Ophthalmology. 2005 May. 112(5):764-70. [Medline].
Nussenblatt RB, Whitcup SM, Palestine AG. Uveitis: Fundamentals and Clinical Practice. 3rd ed. St. Louis: CV Mosby; 2004. 291-300.
Okada AA. Noninfectious uveitis: a scarcity of randomized clinical trials. Arch Ophthalmol. 2005 May. 123(5):682-3. [Medline].
Potter MJ, Myckatyn SO, Maberley AL, et al. Vitrectomy for pars planitis complicated by vitreous hemorrhage: visual outcome and long-term follow-up. Am J Ophthalmol. 2001 Apr. 131(4):514-5. [Medline].
Reinthal EK, Volker M, Freudenthaler N, et al. [Optical coherence tomography in the diagnosis and follow-up of patients with uveitic macular edema]. Ophthalmologe. 2004 Dec. 101(12):1181-8. [Medline].
Smith RE. Pars Planitis. Ryan SJ, ed. Retina. St. Louis: CV Mosby; 1973. Vol. 2: 637-646.
Smith RE, Godfrey WA, Kimura SJ. Chronic cyclitis. I. Course and visual prognosis. Trans Am Acad Ophthalmol Otolaryngol. 1973 Nov-Dec. 77(6):OP760-8. [Medline].
Smith RE, Nozik RA. Uveitis: A Clinical Approach to Diagnosis and Management. 2nd ed. Baltimore: Williams and Wilkins; 1989. 166-170.
Stanford MR, Vaughan RW, Kondeatis E, et al. Are cytokine gene polymorphisms associated with outcome in patients with idiopathic intermediate uveitis in the United Kingdom?. Br J Ophthalmol. 2005 Aug. 89(8):1013-6. [Medline].
Stavrou P, Baltatzis S, Letko E, et al. Pars plana vitrectomy in patients with intermediate uveitis. Ocul Immunol Inflamm. 2001 Sep. 9(3):141-51. [Medline].
Tabbara KF, Al-Kaff AS, Al-Rajhi AA, et al. Heparin Surface-Modified Intraocular Lenses in Patients with Inactive Uveitis or Diabetes. Ophthalmology. 1998. 105(5):843-845. [Medline].
Tessler HH, Fraber MD. Intraocular Lens Implantation Versus no Intraocular Lens Implantation in Patients with Chronic Iridocyclitis and Pars Planitis: A Randomized Prospective Study. Ophthalmology. 1993. 100 (8):1206-1209. [Medline].
Trittibach P, Koerner F, Sarra GM, et al. Vitrectomy for juvenile uveitis: prognostic factors for the long-term functional outcome. Eye. 2006 Feb. 20(2):184-90. [Medline].
Tugal-Tutkun I, Havrlikova K, Power WJ, et al. Changing patterns in uveitis of childhood. Ophthalmology. 1996 Mar. 103(3):375-83. [Medline].
Ozzello DJ, Palestine AG. Factors affecting therapeutic decisions in intermediate and posterior uveitis. Am J Ophthalmol. 2015 Feb. 159 (2):213-20.e3. [Medline].